Colorectal cancer (CRC) is the third most common type of cancer with a worldwide annual incidence of 1.2 million, and mortality rate of approximately 50%. The only available curative treatment for CRC is complete surgical resection of neoplastic tissue (Van Cutsem et al., Colon cancer: Management of locoregional disease, in Kelsen D P, Daly J M, Kern S E, et al (ed): Principles and practice of gastrointestinal oncology. Philadelphia, USA, Lippincott Williams & Wilkins, 2008, pp 581). Determination of the extent of the disease by clinicopathological tumor staging is the primary prognostic factor for CRC patients (Van Cutstem et al., supra). Despite the favorable outcome for patients with localized stage II tumors compared to stage III tumors, more than 20% of stage II patients suffer from recurrence (Gray et al., Lancet 370:2020-2029, 2007). Still, investigations of benefit from adjuvant chemotherapy for stage II patients show conflicting results (Andre et al., Ann Surg Oncol 13:887-898, 2006; Sobrero A, Lancet Oncol 7:515-516, 2006; Kohne, Lancet Oncol 7:516-517, 2006), and surgery remains the only recommended treatment modality (Benson et al., J Clin Oncol 22:3408-3419, 2004). For patients with stage III disease, large clinical trials have consistently showed improved survival with administration of adjuvant chemotherapy, and this constitutes the standard of care for this group of patients (Andre et al., N Engl J Med 350:2343-2351, 2004). However, the significantly poorer survival among patients with stage IIB (T-stage 4, lymph node negative) compared to stage IIIA (T-stage 1-2, lymph node positive) disease, underlines the need for refinements to this prognostic stratification (O'Connell et al., J Natl Cancer Inst 96:1420-1425, 2004).
Accordingly, identification of individual patients in need of adjuvant treatment, primarily by predicting prognosis for stage II and III patients remains a major clinical concern. There are currently no markers in routine clinical use for this purpose (Locker et al., ASCO 2006 J Oncol Pract 24:5313-5327, 2006). Hence, identification of molecular markers for prognostic stratification represents a valuable step towards beneficial personalized management of patients with stage II and III disease.